Human Scar Research Articles

Is Itraconazole Plus Clofazimine an Effective Treatment for Cutaneous Leishmaniasis?

Background: Leishmaniasis is endemic in 88 countries and has a worldwide prevalence of 12 million. Cutaneous leishmaniasis (CL) cases deserve the highest attention due to their magnitude and risk of causing scars in humans. Although several studies have been performed on novel therapies, treatment failure and drug resistance are still common, and most systemic treatments are parenteral. Thus, in this study, it was attempted to find an effective combination oral therapy for this disease. Case Series: Six patients (between 35 and 64 years old) with confirmed CL were treated with a combination of clofazimine (CLZ, 200 mg/d) and itraconazole (ITN, 300 mg/d) for 4 weeks. Then, ITZ 300 mg/d was given for another 4 weeks. All patients were followed up to assess the efficacy and side effects of this treatment regimen. Every single lesion in the patients was remarkably smaller after the course of the treatment (P=0.001), and skin smears became negative. Conclusion: The combination of CLZ and ITN could be a helpful treatment modality in the treatment of CL. However, more and larger studies should be conducted to assess the efficacy and side effects of this combination therapy.

Suture-anchored cutaneous tension induces persistent hypertrophic scarring in a novel murine model.

Hypertrophic scars cause impaired skin appearance and function, seriously affecting physical and mental health. Due to medical ethics and clinical accessibility, the collection of human scar specimens is frequently restricted, and the establishment of scar experimental animal models for scientific research is urgently needed. The four most commonly used animal models of hypertrophic scars have the following drawbacks: the rabbit ear model takes a long time to construct; the immunodeficient mouse hypertrophic scar model necessitates careful feeding and experimental operations; female Duroc pigs are expensive to purchase and maintain, and their large size makes it difficult to produce a significant number of models; and mouse scar models that rely on tension require special skin stretch devices, which are often damaged and shed, resulting in unstable model establishment. Our group overcame the shortcomings of previous scar animal models and created a new mouse model of hypertrophic scarring induced by suture anchoring at the wound edge. We utilized suture anchoring of incisional wounds to impose directional tension throughout the healing process, restrain wound contraction, and generate granulation tissue, thus inducing scar formation. Dorsal paired incisions were generated in mice, with wound edges on the upper back sutured to the rib cage and the wound edges on the lower back relaxed as a control. Macroscopic manifestation, microscopic histological analysis, mRNA sequencing, bioinformatics, and in vitro cell assays were also conducted to verify the reliability of this method. Compared with those in relaxed controls, the fibrotic changes in stretched wounds were more profound. Histologically, the stretched scars were hypercellular, hypervascular, and hyperproliferative with disorganized extracellular matrix deposition, and displayed molecular hallmarks of hypertrophic fibrosis. In addition, the stretched scars exhibited transcriptional overlap with mechanically stretched scars, and human hypertrophic and keloid scars. Phosphatidylinositol 3-kinase-serine/threonine-protein kinase B signaling was implicated as a profibrotic mediator of apoptosis resistance under suture-induced tension. This straightforward murine model successfully induces cardinal molecular and histological features of pathological hypertrophic scarring through localized suture tension to inhibit wound contraction. The model enables us to interrogate the mechanisms of tension-induced fibrosis and evaluate anti-scarring therapies.

MP78-04 PRO-FIBROTIC SERUM CYTOKINES ARE INCREASED IN PATIENTS WITH ANTERIOR URETHRAL STRICTURE DISEASE

You have accessJournal of UrologyCME1 Apr 2023MP78-04 PRO-FIBROTIC SERUM CYTOKINES ARE INCREASED IN PATIENTS WITH ANTERIOR URETHRAL STRICTURE DISEASE Wade Gutierrez, Yi Luo, Denise Juhr, Benjamin Breyer, Sean Elliott, Jeremy Myers, Alex Vanni, Katherine Christel, Laila Dahmoush, and Bradley Erickson Wade GutierrezWade Gutierrez More articles by this author , Yi LuoYi Luo More articles by this author , Denise JuhrDenise Juhr More articles by this author , Benjamin BreyerBenjamin Breyer More articles by this author , Sean ElliottSean Elliott More articles by this author , Jeremy MyersJeremy Myers More articles by this author , Alex VanniAlex Vanni More articles by this author , Katherine ChristelKatherine Christel More articles by this author , Laila DahmoushLaila Dahmoush More articles by this author , and Bradley EricksonBradley Erickson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003355.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Anterior urethral stricture disease (aUSD) is a heterogeneous condition with complex pathophysiology. Little is known about systemic factors predisposing to or resulting from stricture formation. To address this gap in knowledge, we assessed levels of 27 cytokines in serum from patients with and without strictures. We hypothesized that patients with strictures would have distinct serum cytokine profiles relative to controls. METHODS: Five centers prospectively enrolled patients into an NIDDK-funded study evaluating local and systemic inflammatory patterns in aUSD. Subjects underwent standard urethroplasty per surgeon routine and tissue was sent to a centralized tissue repository. Serum was collected prior to stricture repair. Levels of 27 cytokines were assessed by ELISA. H&E-stained sections of stricture tissue were examined by a single, blinded pathologist and evaluated for the presence or absence of inflammation. RESULTS: Patient-matched serum and stricture specimens were collected from 113 subjects. Strictures were grouped based on the presence or absence of inflammation (n=66 and n=47, respectively). Serum from age-matched patients without urethral strictures was used as a control (n=9). Four pro-fibrotic cytokines were significantly increased in patients with strictures: interleukin-9 (IL-9), platelet derived growth factor-BB (PDGF-BB), C-C Motif Chemokine Ligand 4 (CCL4), and C-C Motif Chemokine Ligand 5 (CCL5) [A-D]. Only IL-9 levels differed by stricture inflammatory pattern (890.4 ng/mL vs 773.0 ng/mL, p<0.05). In addition to higher levels of pro-fibrotic cytokines, interleukin-1 receptor antagonist (IL-1Ra), which has immunosuppressive functions, was increased in patients with strictures [E]. CONCLUSIONS: Patients with aUSD have unique serum cytokine profiles relative to age-matched controls. Four of these cytokines, IL-9, PDGF-BB, CCL4, and CCL5 have previously been implicated in promoting fibrosis and scarring in humans and in animal models. IL-1Ra has immunosuppressive functions and may be increased to maintain homeostasis. Further studies are needed to determine if these cytokines are increased as a result of the stricture or if their levels are higher at baseline, predisposing patients to stricture formation. Source of Funding: NIDDK 1R21DK115945-01 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1132 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wade Gutierrez More articles by this author Yi Luo More articles by this author Denise Juhr More articles by this author Benjamin Breyer More articles by this author Sean Elliott More articles by this author Jeremy Myers More articles by this author Alex Vanni More articles by this author Katherine Christel More articles by this author Laila Dahmoush More articles by this author Bradley Erickson More articles by this author Expand All Advertisement PDF downloadLoading ...

Establishing a Xenograft Model with CD-1 Nude Mice to Study Human Skin Wound Repair.

A significant gap exists in the translatability of small-animal models to human subjects. One important factor is poor laboratory models involving human tissue. Thus, the authors have created a viable postnatal human skin xenograft model using athymic mice. Discarded human foreskins were collected following circumcision. All subcutaneous tissue was removed from these samples sterilely. Host CD-1 nude mice were then anesthetized, and dorsal skin was sterilized. A 1.2-cm-diameter, full-thickness section of dorsal skin was excised. The foreskin sample was then placed into the full-thickness defect in the host mice and sutured into place. Xenografts underwent dermal wounding using a 4-mm punch biopsy after engraftment. Xenografts were monitored for 14 days after wounding and then harvested. At 14 days postoperatively, all mice survived the procedure. Grossly, the xenograft wounds showed formation of a human scar at postoperative day 14. Hematoxylin and eosin and Masson trichome staining confirmed scar formation in the wounded human skin. Using a novel artificial intelligence algorithm using picrosirius red staining, scar formation was confirmed in human wounded skin compared with the unwounded skin. Histologically, CD31 + immunostaining confirmed vascularization of the xenograft. The xenograft exclusively showed human collagen type I, CD26 + , and human nuclear antigen in the human scar without any staining of these human markers in the murine skin. The proposed model demonstrates wound healing to be a local response from tissue resident human fibroblasts and allows for reproducible evaluation of human skin wound repair in a preclinical model. Radiation-induced fibrosis is a widely prevalent clinical phenomenon without a well-defined treatment at this time. This study will help establish a small-animal model to better understand and develop novel therapeutics to treat irradiated human skin.

The Secretome of Irradiated Peripheral Mononuclear Cells Attenuates Hypertrophic Skin Scarring.

Hypertrophic scars can cause pain, movement restrictions, and reduction in the quality of life. Despite numerous options to treat hypertrophic scarring, efficient therapies are still scarce, and cellular mechanisms are not well understood. Factors secreted by peripheral blood mononuclear cells (PBMCsec) have been previously described for their beneficial effects on tissue regeneration. In this study, we investigated the effects of PBMCsec on skin scarring in mouse models and human scar explant cultures at single-cell resolution (scRNAseq). Mouse wounds and scars, and human mature scars were treated with PBMCsec intradermally and topically. The topical and intradermal application of PBMCsec regulated the expression of various genes involved in pro-fibrotic processes and tissue remodeling. We identified elastin as a common linchpin of anti-fibrotic action in both mouse and human scars. In vitro, we found that PBMCsec prevents TGFβ-mediated myofibroblast differentiation and attenuates abundant elastin expression with non-canonical signaling inhibition. Furthermore, the TGFβ-induced breakdown of elastic fibers was strongly inhibited by the addition of PBMCsec. In conclusion, we conducted an extensive study with multiple experimental approaches and ample scRNAseq data demonstrating the anti-fibrotic effect of PBMCsec on cutaneous scars in mouse and human experimental settings. These findings point at PBMCsec as a novel therapeutic option to treat skin scarring.

Anagen hair follicles transplanted into mature human scars remodel fibrotic tissue

Despite the substantial impact of skin scarring on patients and the healthcare system, there is a lack of strategies to prevent scar formation, let alone methods to remodel mature scars. Here, we took a unique approach inspired by how healthy hairbearing skin undergoes physiological remodelling during the regular cycling of hair follicles. In this pilot clinical study, we tested if hair follicles transplanted into human scars can facilitate tissue regeneration and actively remodel fibrotic tissue, similar to how they remodel the healthy skin. We collected full-thickness skin biopsies and compared the morphology and transcriptional signature of fibrotic tissue before and after transplantation. We found that hair follicle tranplantation induced an increase in the epidermal thickness, interdigitation of the epidermal-dermal junction, dermal cell density, and blood vessel density. Remodelling of collagen type I fibres reduced the total collagen fraction, the proportion of thick fibres, and their alignment. Consistent with these morphological changes, we found a shift in the cytokine milieu of scars with a long-lasting inhibition of pro-fibrotic factors TGFβ1, IL13, and IL-6. Our results show that anagen hair follicles can attenuate the fibrotic phenotype, providing new insights for developing regenerative approaches to remodel mature scars.

Comparison of the efficacy of seven types of microneedles for treating a rabbit hypertrophic scar model.

Microneedle technology can effectively suppress the formation of hypertrophic scarring in both animals and humans. Our previous research has revealed that this is due to the physical contact inhibition effect by using microneedles made of liquid-crystal polymers as the model device. One important factor we didn't study is the influence of the fabrication materials of microneedles. Therefore, this article examines this key point on a rabbit ear hypertrophic scar model. We monitor the thickness of the scars, and the expression of α-SMA and Ki-67 protein, and TGF-β1 mRNA in a period of 42 days. Among microneedles made of 6 polymeric materials and stainless steel, polymethylmethacrylate microneedles present superiority in all aspects including the reduction of tissue fibrosis, and the expression of α-SMA, Ki-67 protein and TGF-β1 mRNA. On the other hand, polycarbonates, polyurethane, and polylactic-co-glycolic acid microneedles could suppress three biomarker expressions.

A volar skin excisional wound model for in situ evaluation of multiple-appendage regeneration and innervation.

Promoting rapid wound healing with functional recovery of all skin appendages is the main goal of regenerative medicine. So far current methodologies, including the commonly used back excisional wound model (BEWM) and paw skin scald wound model, are focused on assessing the regeneration of either hair follicles (HFs) or sweat glands (SwGs). How to achieve de novo appendage regeneration by synchronized evaluation of HFs, SwGs and sebaceous glands (SeGs) is still challenging. Here, we developed a volar skin excisional wound model (VEWM) that is suitable for examining cutaneous wound healing with multiple-appendage restoration, as well as innervation, providing a new research paradigm for the perfect regeneration of skin wounds. Macroscopic observation, iodine-starch test, morphological staining and qRT-PCR analysis were used to detect the existence of HFs, SwGs, SeGs and distribution of nerve fibres in the volar skin. Wound healing process monitoring, HE/Masson staining, fractal analysis and behavioral response assessment were performed to verify that VEWM could mimic the pathological process and outcomes of human scar formation and sensory function impairment. HFs are limited to the inter-footpads. SwGs are densely distributed in the footpads, scattered in the IFPs. The volar skin is richly innervated. The wound area of the VEWM at 1, 3, 7 and 10days after the operation is respectively 89.17% ± 2.52%, 71.72% ± 3.79%, 55.09 % ± 4.94% and 35.74% ± 4.05%, and the final scar area accounts for 47.80% ± 6.22% of the initial wound. While the wound area of BEWM at 1, 3, 7 and 10 days after the operation are respectively 61.94% ± 5.34%, 51.26% ± 4.89%, 12.63% ± 2.86% and 6.14% ± 2.84%, and the final scar area accounts for 4.33% ± 2.67% of the initial wound. Fractal analysis of the post-traumatic repair site for VEWM vs human was performed: lacunarity values, 0.040 ± 0.012 vs 0.038 ± 0.014; fractal dimension values, 1.870 ± 0.237 vs 1.903 ± 0.163. Sensory nerve function of normal skin vs post-traumatic repair site was assessed: mechanical threshold, 1.05 ± 0.52 vs 4.90g ± 0.80; response rate to pinprick, 100% vs 71.67% ± 19.92%, and temperature threshold, 50.34°C ± 3.11°C vs 52.13°C ± 3.54°C. VEWM closely reflects the pathological features of human wound healing and can be applied for skin multiple-appendages regeneration and innervation evaluation.

Disrupting mechanotransduction decreases fibrosis and contracture in split-thickness skin grafting.

Burns and other traumatic injuries represent a substantial biomedical burden. The current standard of care for deep injuries is autologous split-thickness skin grafting (STSG), which frequently results in contractures, abnormal pigmentation, and loss of biomechanical function. Currently, there are no effective therapies that can prevent fibrosis and contracture after STSG. Here, we have developed a clinically relevant porcine model of STSG and comprehensively characterized porcine cell populations involved in healing with single-cell resolution. We identified an up-regulation of proinflammatory and mechanotransduction signaling pathways in standard STSGs. Blocking mechanotransduction with a small-molecule focal adhesion kinase (FAK) inhibitor promoted healing, reduced contracture, mitigated scar formation, restored collagen architecture, and ultimately improved graft biomechanical properties. Acute mechanotransduction blockade up-regulated myeloid CXCL10-mediated anti-inflammation with decreased CXCL14-mediated myeloid and fibroblast recruitment. At later time points, mechanical signaling shifted fibroblasts toward profibrotic differentiation fates, and disruption of mechanotransduction modulated mesenchymal fibroblast differentiation states to block those responses, instead driving fibroblasts toward proregenerative, adipogenic states similar to unwounded skin. We then confirmed these two diverging fibroblast transcriptional trajectories in human skin, human scar, and a three-dimensional organotypic model of human skin. Together, pharmacological blockade of mechanotransduction markedly improved large animal healing after STSG by promoting both early, anti-inflammatory and late, regenerative transcriptional programs, resulting in healed tissue similar to unwounded skin. FAK inhibition could therefore supplement the current standard of care for traumatic and burn injuries.

A Systematic Review Comparing Animal and Human Scarring Models.

IntroductionA reproducible, standardised model for cutaneous scar tissue to assess therapeutics is crucial to the progress of the field. A systematic review was performed to critically evaluate scarring models in both animal and human research.MethodAll studies in which cutaneous scars are modelling in animals or humans were included. Models that were focused on the wound healing process or those in humans with scars from an existing injury were excluded. Ovid Medline® was searched on 25 February 2019 to perform two near identical searches; one aimed at animals and the other aimed at humans. Two reviewers independently screened the titles and abstracts for study selection. Full texts of potentially suitable studies were then obtained for analysis.ResultsThe animal kingdom search yielded 818 results, of which 71 were included in the review. Animals utilised included rabbits, mice, pigs, dogs and primates. Methods used for creating scar tissue included sharp excision, dermatome injury, thermal injury and injection of fibrotic substances. The search for scar assessment in humans yielded 287 results, of which 9 met the inclusion criteria. In all human studies, sharp incision was used to create scar tissue. Some studies focused on patients before or after elective surgery, including bilateral breast reduction, knee replacement or midline sternotomy.DiscussionThe rabbit ear scar model was the most popular tool for scar research, although pigs produce scar tissue which most closely resembles that of humans. Immunodeficient mouse models allow for in vivo engraftment and study of human scar tissue, however, there are limitations relating to the systemic response to these xenografts. Factors that determine the use of animals include cost of housing requirements, genetic traceability, and ethical concerns. In humans, surgical patients are often studied for scarring responses and outcomes, but reproducibility and patient factors that impact healing can limit interpretation. Human tissue use in vitro may serve as a good basis to rapidly screen and assess treatments prior to clinical use, with the advantage of reduced cost and setup requirements.

In Vitro, Ex Vivo, and In Vivo Approaches for Investigation of Skin Scarring: Human and Animal Models.

Significance: The cutaneous repair process naturally results in different types of scarring that are classified as normal or pathological. Affected individuals are often affected from an esthetic, physical (functional), and psychosocial perspective. The distinct nature of scarring in humans, particularly the formation of pathological scars, makes the study of skin scarring a challenge for researchers in this area. Several established experimental models exist for studying scar formation. However, the increasing development and validation of newly emerging models have made it possible to carry out studies focused on different variables that influence this unique process. Recent Advances: Experimental models such as in vitro, ex vivo, and in vivo models have obtained different degrees of success in the reproduction of the scar formation in its native milieu and true environment. These models also differ in their ability to elucidate the molecular, cellular, and structural mechanisms involved in scarring, as well as for testing new agents and approaches for therapies. The models reviewed here, including cells derived from human skin and in vivo animal models, have contributed to the advancement of skin scarring research. Critical Issues and Future Directions: The absence of experimental models that faithfully reproduce the typical characteristics of the different types of human skin scars makes the improvement of validated models and the establishment of new ones a critical unmet need. The fields of wound healing research combined with tissue engineering have offered newer alternatives for experimental studies with the potential to provide clinically useful knowledge about scar formation.

Oxymatrine promotes hypertrophic scar repair through reduced human scar fibroblast viability, collagen and induced apoptosis via autophagy inhibition.

Scars are common complications of burns and trauma, resulting in mental trauma, physical pain, and a heavy financial burden for patients. Specific and effective anti‐scarring drugs are lacking in clinical practice. Phytochemicals are easily accessible, low in toxicity, and have various biological and pharmacological properties. Oxymatrine is a phytochemical that regulates autophagy networks. Autophagy is closely related to the maintenance, activity, differentiation, and life‐death of skin fibroblasts during wound repair, which results in pathological scars. We hypothesised that oxymatrine may promote hypertrophic scar repair by inhibiting fibroblast autophagy. In vitro studies showed that inhibition of autophagy by oxymatrine decreased viability and collagen metabolism, and increased apoptosis of human scar fibroblasts (HSFs). In vivo studies showed that inhibition of autophagy by oxymatrine promoted scar repair, resulting in a significantly improved final outcome of the hypertrophic scars, a smaller scar area, decreased epidermal and dermal thickness, and a significant downregulation of CK10, P63, collagen I, α‐SMA, and TGF‐β1. In summary, oxymatrine promoted hypertrophic scar repair by decreasing HSF viability and collagen, and inducing apoptosis via autophagy inhibition. This study provides a new perspective on the mechanism of hypertrophic burn scar formation, as well as key scientific data for the application of the phytochemical oxymatrine as a new method for the prevention and treatment of hypertrophic scars.

A Methylome and Transcriptome Analysis of Normal Human Scar Cells Reveals a Role for FOXF2 in Scar Maintenance

Scars are maintained for life and increase in size during periods of growth such as puberty. Epigenetic changes in fibroblasts after injury may underpin the maintenance and growth of scars. In this study, we combined methylome and transcriptome data from normotrophic mature scar and contralateral uninjured normal skin fibroblasts to identify potential regulators of scar maintenance. In total, 219 significantly differentially expressed and 1,199 significantly differentially methylated promoters were identified, of which there were 12 genes both significantly differentially methylated and expressed. Of these, the two transcription factors, FOXF2 and MKX, were selected for further analysis. Immunocytochemistry and qPCR suggested that FOXF2 but not MKX had elevated expression in scar fibroblasts. Using RNA sequencing, FOXF2 knockdown was shown to significantly reduce the expression of extracellular matrix‒related genes, whereas MKX did not appear to affect similar pathways. Finally, FOXF2 knockdown was also shown to significantly decrease collagen I production in scar and keloid fibroblasts. This study provides insights into the maintenance of normotrophic scar, suggesting that FOXF2 is an important regulator of this process. Targeting genes responsible for maintenance of scar phenotype may ameliorate scar appearance and improve patient outcomes in the future.

MicroRNA-181a promotes the proliferation of hypertrophic scar fibroblasts and inhibits their apoptosis via targeting phosphatase and tensin homolog.

This study aimed to compare the expression of microRNA (miR)-181a and phosphatase and tensin homolog (PTEN) in hypertrophic scar tissue and cells and to explore the effects of miR-181a and PTEN on the proliferation and apoptosis of the human scar fibroblast cell line HSFb. HSFb cells were transfected with miR-negative control (miR-NC), miR-181a mimics, miR-181a inhibitor, pcDNA3.1-PTEN (pc-PTEN), or small interfence-PTEN (si-PTEN) plasmid using a Lipofectamine 2000 transfection kit. The effects of miR-181a and PTEN on the proliferation and apoptosis of HSFb were determined using a Cell Counting Kit (CCK)-8 experiment and flow cytometry, respectively. The effects of miR-181a and PTEN on the expression of apoptosis-related proteins in HSFb, including type I collagen (Col-1) and type III collagen (Col-3), were measured by western blot. Finally, the relationship between miR-181a and PTEN was explored by the dual-luciferase reporter gene experiment. The miR-181a in hypertrophic scar tissues and HSFb were significantly up-regulated compared to embryo skin fibroblast (ESF-1) cells and normal tissues (P<0.05), whereas the opposite results were seen for PTEN expression (P<0.05). Inhibiting miR-181a or upregulating the expression of PTEN significantly suppressed the proliferation of HSFb (P<0.05) and induced their apoptosis (P<0.05). Western blot revealed that inhibiting and upregulating miR-181a and PTEN, respectively, decreased the expression of the B-cell lymphoma-2 (Bcl-2), Col-1, and Col-3 proteins in HSFb, but significantly up-regulated the expression of Bcl-2-associated X protein (Bax), cleaved caspase-3 (c-caspase-3), and cleaved caspase-9 (c-caspase-9) (P<0.05). The dual-luciferase reporter gene experiment results confirmed PTEN to be the downstream target gene of miR-181a. Simultaneous upregulation of miR-181a and PTEN expression had no significant effect on the proliferation and apoptosis of HSFb. miR-181a promotes the up-regulation of Col-1 and Col-3, and regulates the proliferation and apoptosis of HSFb by targeting PTEN, thereby enhancing the formation of hypertrophic scarring (HS). Therefore, miR-181a and PTEN may be potential therapeutic targets for the treatment of HS.

Educational Intervention and Early Marriages Reductions in North ‘A’ District- Unguja

High prevalence of early marriage is the most common problem worldwide, which also is reported among Zanzibar girls. This problem constitutes a gross violation of human rights, leaving physical, psychological and emotional scars for life. The aim of this study was to assess the educational interventions and early marriage reduction in North “A” District Unguja. The emphasis was to identify the contributions of educational regulations, publicity and new syllabus on reducing early marriage rate. In this study, 90 participants were selected among Teachers and District officers. The study used quantitative approach. Primary data were collected using questionnaires and analysis was done using descriptive analysis and regression. Simple random Sampling was deployed. The study has revealed that, educational interventions are a major strategy in protecting early marriage in North ‘A’ District. Publicity reduces early marriage in the community through information and knowledge provided by using media like Television, radio and publication and also new syllabus had impact in reducing early marriage when students receive knowledge about cross cutting issues and then this knowledge shared in the society, more over there is a greater contribution of educational regulations in reducing early marriage due to different opportunity obtained in this regulations for the pupils. Key words: Marriage, Early marriage, Interventions, Educational Interventions. DOI: 10.7176/RHSS/11-6-03 Publication date: March 31 st 2021

Association between MeCP2 and Smad7 in the pathogenesis and development of pathological scars

To explore the relationship between methylated binding protein 2 (MeCP2) and mothers against decapentaplegic homolog 7 (Smad7) in the pathogenesis and development of pathological scars. Immunohistochemistry, Western blot and real-time polymerase chain reaction (RT-PCR) were used to detect the expression of MeCP2 in different types of human scars and hypertrophic scars at different growth times. The methylation status of Smad7 gene promoter in different scar tissues was determined by methylation-specific PCR. After transfection with MeCP2-siRNA (small interfering RNA) in human keloid fibroblasts, MTT assay was used to assess the proliferation activity of keloid fibroblasts, while RT-PCR and Western blot assays were used to detect the expression levels of MeCP2, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), phospho-Smad2 (p-Smad2) and Smad7. MeCP2 was mainly expressed in the nucleus of fibroblasts. The mRNA and protein levels of MeCP2 were significantly higher in keloids than in hypertrophic scars, normal scars and normal skin (p<.05). The expression level of MeCP2 in hypertrophic scars during the growth period of <6 months was markedly higher than that of >6 months (p<.05). The methylation level of Smad7 was significantly higher in keloids compared to normal skin. After MeCP2 silencing, the proliferation rate of human keloid fibroblasts was decreased, the mRNA and protein levels of Smad7 were increased, and the expression levels of TGF-β1, α-SMA and p-Smad2 were decreased (p<.05). MeCP2 and Smad7 play an important role in formation of pathological scars. During keloid formation, MeCP2 weakens the inhibitory effect of Smad7 on p-Smad2/3 by downregulating the expression of Smad7, which in turn promotes fibrosis and scar hyperplasia.

Anagen Hair Follicles Transplanted into Mature Human Scars Remodel Fibrotic Tissue

Despite the substantial impact of skin scarring on patients and the healthcare system, there is a lack of strategies to prevent scar formation, let alone methods to remodel mature scars. Here, we took a unique approach inspired by how healthy hair‑bearing skin undergoes physiological remodeling during the regular cycling of hair follicles. In a pilot clinical study, we tested if anagen hair follicles transplanted into human scars can actively remodel fibrotic tissue, similar to how they remodel the healthy skin. We collected full‑thickness skin biopsies and compared the morphology and transcriptional signature of fibrotic tissue before and after transplantation. We found that anagen hair follicles induced an increase in the epidermal thickness, interdigitation of the epidermal‑dermal junction, dermal cell density, and vessel density. Remodeling of collagen type I fibres reduced the total collagen fraction, the proportion of thick fibers, and their alignment. Consistent with these morphological changes, we found a shift in the cytokine milieu of scars with a long-lasting inhibition of pro‑fibrotic factors TGF‑β1, IL‑13, and IL-6. Our results show that anagen hair follicles can attenuate the fibrotic phenotype, providing new insights for developing therapeutic approaches to remodel mature scars.

Mast Cells in Skin Scarring: A Review of Animal and Human Research.

Mast cells (MCs) are an important immune cell type in the skin and play an active role during wound healing. MCs produce mediators that can enhance acute inflammation, stimulate re-epithelialisation as well as angiogenesis, and promote skin scarring. There is also a link between MCs and abnormal pathological cutaneous scarring, with increased numbers of MCs found in hypertrophic scars and keloid disease. However, there has been conflicting data regarding the specific role of MCs in scar formation in both animal and human studies. Whilst animal studies have proved to be valuable in studying the MC phenomenon in wound healing, the appropriate translation of these findings to cutaneous wound healing and scar formation in human subjects remains crucial to elucidate the role of these cells and target treatment effectively. Therefore, this perspective paper will focus on evaluation of the current evidence for the role of MCs in skin scarring in both animals and humans in order to identify common themes and future areas for translational research.

The Northwestern Abdominoplasty Scar Model: A Tool for High-Throughput Assessment of Scar Therapeutics.

Significance: Scar management is an important concern in plastic surgery. Scar models that best mimic in vivo human scarring are essential for understanding scar development and progression, assessing the efficacy of therapeutics, and providing reliable and valid research outcomes. Recent Advances: In 2016, Lanier et al. proposed a new in vivo patient model, the Northwestern Abdominoplasty Scar Model, that overcomes the prior limitations of both animal and human models, with greater representativeness of the human scarring process, expedited recruitment, smaller sample requirements, and greater flexibility in the types and number of interventions that can be studied simultaneously. Critical Issues: Existing animal models suffer from limitations that impede generalization to human scars. Human scar studies are difficult to conduct and rarely used due to recruitment difficulties, ethical concerns regarding purposeful wounding, and inherent variability based on location, type of scar, and the heterogeneity of the host response between humans. Although overcoming many of these hurdles, the Northwestern Abdominoplasty Scar Model still has a few limitations. In addition, there remains a need for further study of and comparison between the Northwestern Abdominoplasty Scar Model and existing human and animal models, to inspire more widespread acceptance of a standardized human scar model. Future Directions: The Northwestern Abdominoplasty Scar Model is a critical stepping stone toward better human scar models. This model hopefully will inspire other in vivo patient models utilizing elective surgery to overcome recruitment and ethical concerns.

A highly simulated scar model developed by grafting human thin split-thickness skin on back of nude mouse: The remodeling process, histological characteristics of scars

A predictive scar animal model is needed in order to study the mechanism and assess the therapies before its use in humans. However, due to the differences in wound healing patterns and regeneration ability, none of the existing models can fully simulate the characteristics of human scar. The aim of this study was to build a model that recapitulated the developing process and outcomes of human hypertrophic scar (HS). Nude mice were grafted with thin split-thickness human skins. The dynamic changes and final outcomes of the grafts were investigated. The results showed that human skin grafts survived and underwent progressive scarring remodeling in morphology and histology. Scar related markers (α-SMA, CD34, Collage I, TGF-β1) were positive in immunohistology. Protein expressions in TGF-β1/Smad2/3 pathway were increased in accordance with HS during the development process by western blotting. It was finally proved that scar reconstructed by this model matches a real-world human HS. This is a stable, easy to reproduce model for studying the scar formation process and its properties.